Tumor expression of miR-34a-3p is an independent predictor of recurrence in non-muscle-invasive bladder cancer and promising additional factor to improve predictive value of EORTC nomogram
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Validation Study
PubMed
30446443
DOI
10.1016/j.urolonc.2018.10.014
PII: S1078-1439(18)30397-1
Knihovny.cz E-resources
- Keywords
- Non–muscle invasive bladder cancer, Recurrence, miR-34-3p, microRNA,
- MeSH
- Cystectomy methods MeSH
- Cystoscopy methods MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local diagnosis genetics prevention & control MeSH
- MicroRNAs metabolism MeSH
- Urinary Bladder pathology surgery MeSH
- Biomarkers, Tumor metabolism MeSH
- Urinary Bladder Neoplasms genetics mortality surgery MeSH
- Nomograms * MeSH
- Predictive Value of Tests MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN34 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
OBJECTIVES: Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease characterized by a high primary tumor recurrence rate. Current prognostic systems used for predicting recurrence in individual patients have limitations and do not consider the biological background of this tumor type. Our study aimed to find microRNAs (miRNAs) associated with NMIBC recurrence. METHODS: Seventy-eight NMIBC patients were prospectively enrolled and divided into exploratory and validation cohorts. Out of these patients, 32 developed recurrence within 18 months after surgery, while 46 did not show any sign of recurrence after 30 months. Expression profiles of 2,578 miRNAs were obtained using Affymetrix miRNA microarrays and candidate miRNAs validated using the individual quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: The expression profiling revealed a set of 137 miRNAs differentially expressed between NMIBC patients with and without recurrence (P < 0.05). In the validation phase, miR-34a-3p had a significantly higher expression in tumors of NMIBC patients without recurrence (P = 0.0155). Decreased expression of miR-34a-3p was associated with significantly shorter recurrence-free survival (P = 0.009). Cox regression analysis confirmed that miR-34a-3p is an independent biomarker associated with a lower risk of recurrence (hazard ratio (HR) = 0.3184, 95% confidence interval = 0.003-0.681, P = 0.0258). Combination of miR-34a-3p and European Organization for Research and Treatment of Cancer risk score into one predictive model enabled to predict individual risk of recurrence with high statistical significance and analytical performance (P < 0.0001; area under curve = 0.8368; sensitivity 83%, and specificity 75%). CONCLUSIONS: Our data suggest that miR-34a-3p is an independent biomarker of NMIBC recurrence and a promising candidate for further independent validations as an additional factor to improve predictive value of European Organization for Research and Treatment of Cancer nomogram.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Urologic Oncology Masaryk Memorial Cancer Institute Brno Czech Republic
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